Klinefelter syndrome

Klinefelter syndrome (KS) is a genetic condition resulting from an additional X chromosome in phenotypic males (47,XXY). KS affects ∼1 in 600 males however historically only ∼25% are accurately diagnosed in their lifetime. Testicular development and function are impaired, often resulting in hypergonadotropic hypogonadism and the classic physical phenotype of small testes, gynecomastia, and azoospermia. Testosterone replacement is standard treatment, however there is practice variability on when to initiate this therapy. Other frequently associated manifestations include mild developmental delays, language-based learning disabilities and disorders of insulin resistance which add to the increased morbidity and mortality in this condition. There are multiple mechanisms proposed for how the additional X chromosome results in the physical phenotype of KS and the heterogeneity among affected individuals. Recent advances in KS include early diagnosis identified through prenatal cell free DNA screening and successful retrieval of viable sperm through testicular sperm extraction.